Primary Outcomes

PCR ratios of Bcr-Abl/Abl (molecular CR) after 12 months of therapy with Nilotinib

time frame:
12 months

Secondary Outcomes

Measure

Complete Cytogenetic Response

time frame:
6 months

Eligibility Criteria

Male or female participants at least 16 years old.

Inclusion Criteria:
1. Diagnosis of Ph-positive or Bcr-positive CML in early chronic phase CML (i.e., time
from diagnosis 12 months). Except for hydroxyurea, patients must have received no or
minimal prior therapy, defined as <1 month (30 days) of prior interferon-alpha (with
or without cytarabine) and/or an FDA-approved TKI. Patients with de novo accelerated
phase will be treated but analyzed separately.
2. Age >/= 16 years (Age >18 years to participate in optional symptom burden assessment)
3. ECOG performance of 0-2.
4. Adequate end organ function, defined as the following: total bilirubin < 1.5 x ULN,
SGPT < 2.5 x ULN, creatinine < 1.5 x ULN.
5. Patients must sign an informed consent indicating they are aware of the
investigational nature of this study, in keeping with the policies of the hospital.
6. Reliable telephone access to receive calls from an interactive voice response system
(IVR) (only applicable to patients who will participate in optional symptom burden
assessment).
Exclusion Criteria:
1. NYHA cardiac class 3-4 heart disease as well as impaired cardiac function defined as:
LVEF < 45% as determined by MUGA scan or electrocardiogram; Complete left bundle
branch block; Use of cardiac pacemaker; ST depression of > 1 mm in 2 or more leads
and/or T wave inversions in 2 or more continuous leads; Congenital long QT syndrome;
History of, or presence of significant ventricular or atrial tachyarrhythmia's;
Clinically significant resting bradycardia (< 50 bpm); QTc > 450 msec on screening
ECG (using the QTcF formula);
2. (Continued from #1) Right bundle branch block plus left anterior hemiblock,
bivascular block; Myocardial infarction within 12 months prior to starting AMN107;
Unstable angina diagnosed or treated within the past 12 months; Other clinically
significant heart disease (e.g. congestive heart failure, uncontrolled hypertension,
history of labile hypertension, or history of poor compliance with an
antihypertensive regimen).
3. Patients with active, uncontrolled psychiatric disorders including: psychosis, major
depression, and bipolar disorders.
4. Female patients of childbearing potential must have negative pregnancy test within 7
days before initiation of study drug dosing. Postmenopausal women must be amenorrheic
for at least 12 months to be considered of non-childbearing potential. Surgical
sterilization is considered non-childbearing potential. Female patients of
reproductive potential must agree to employ an effective method of birth control
(hormonal or barrier) throughout the study and for up to 3 months following
discontinuation of study drug.
5. Patients with severe and/or uncontrolled medial disease (i.e., uncontrolled diabetes,
chronic renal disease, or active uncontrolled infection [persistent fever and
worsening clinical condition]).
6. Patient with known chronic liver disease (i.e., chronic active hepatitis, and
cirrhosis).
7. Patient with known diagnosis of human immunodeficiency virus (HIV) infection.
8. Patients in late chronic phase (i.e., time from diagnosis to treatment >12 months) or
blastic phase are excluded. The definitions of CML phases are as follows: A. Early
chronic phase: time from diagnosis to therapy < 12 months Late chronic phase: time
from diagnosis to therapy > 12 months.B. Blastic phase: presence of 30% blasts or
more in the peripheral blood or bone marrow. C. Accelerated phase CML: presence of
any of the following features: * Peripheral or marrow blasts 15% or more.
9. (Cont. #8)Peripheral or marrow basophils 20% or more. *Thrombocytopenia < 100 x
10(9)/L unrelated to therapy. * Documented extramedullary blastic disease outside
liver or spleen due to past causes D. Clonal evolution defined as the presence of
additional chromosomal abnormalities other than the Ph chromosome is part of
accelerated phase CML. Ph chromosome variants or complex Ph chromosome translocations
are not considered to indicate disease acceleration.
10. ( Cont # 8) We have recently found clonal evolution to have a variable prognostic
impact and may be suppressed with IFN-a therapy. Hence these patients, like others
with de novo accelerated phase, will be eligible, and analyzed separately.

Additional Information

Nilotinib is a drug that is designed to block a protein that is responsible for the
development of CML.
If you are found to be eligible to take part in this study, you will take 2-4 nilotinib
capsules or tablets by mouth 2 times a day (4-8 capsules or tablets a day total) every day,
at least 8 hours apart. Nilotinib should be taken each morning and evening with a large
glass of water. The study medication will be given to you every 3 - 12 months. You will
also be given a "pill diary" to write down when (day and time) you take the drug. You will
also write in the diary any side effects you may experience. You should bring the diary,
any unused capsules or tablets, and empty containers of nilotinib with you to every visit to
the study doctor. Any unused supplies must be returned at the end of the study.
Every 1-4 weeks during the first 4 weeks of the study, you will have around 2 teaspoons of
blood drawn for routine blood tests. The blood tests will then be repeated every 4-8 weeks
(or more often if your doctor feels it is necessary) until you have been on study for 6
months, then every 3 to 6 months for another 18 months. After that, you may have the blood
tests repeated as often as the doctor thinks it is needed. A bone marrow sample will also
be taken every 3-4 months for the first year and then every 6-12 months in the 2nd year,
then every 2-3 years for as long as you are on the study to check on the status of the
disease. Additionally, blood (about ½ tablespoon) will be drawn or a bone marrow sample will
be collected every 3-4 months for the first year and then every 6-12 months until 2 years,
and then about one time a year for as long as you are on the study to check on the status of
the disease. However, if you are in complete remission after Year 2, your doctor will
decide when you will have a bone marrow aspiration. But you will still have blood drawn
(about ½ tablespoon) every 1 - 3 years to check the status of your disease. An ECG will be
repeated around Day 5, and then at about 6 weeks and about 3 months.
You will be asked to visit the doctor for a physical exam and to have vital signs measured
periodically. These visits will be scheduled at least every 3 to 4 months the first year.
After the first year, the study staff will recommend that you have physical exams once every
year. The visits may be scheduled more often depending on the status of the disease.
Treatment may be continued for up to 8-10 years or as long as the doctor feels it is
necessary to control the leukemia. If the disease gets worse or you experience any
intolerable side effects, you will be taken off the study and your doctor will discuss other
treatment options with you.
This is an investigational study. Nilotinib is FDA approved. A total of 150 patients will
take part in this study. All will be enrolled at MD Anderson.

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